Inhibition of methemoglobin and metmyoglobin reduction by cobalt

Hagler, Louis; Coppes, R. I.

doi:10.1016/0006-2952(82)90684-0

Cited by 8 publications

(6 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The physiological function of Mb has been regarded for some time to be facilitation of the diffusion of dioxygen in skeletal and cardiac muscle tissue [1][2][3] though discovery that a mouse devoid of myoglobin exhibits a surprisingly mild phenotype [4] has stimulated further consideration of this subject [5][6][7][8]. Mb is readily autoxidized to metMb in an aerobic environment (reviewed in [9]), and enzymatic reduction of myoglobin to the reduced, Fe(II) state was reported over twenty years ago [10] though the subsequent literature has produced inconsistent results regarding the nature of this enzymatic system (reviewed in [11]). The literature concerning the oxidation-reduction properties and electron transfer kinetics of myoglobin is extensive (a review of the older literature is provided in [12]) and in more recent years has emphasized the use of myoglobin as (i) a model for studies of intramolecular electron transfer (e.g., [13,14]), (ii) a participant in protein-protein electron transfer reactions (e.g., [15][16][17][18]), a model for ligand binding (e.g., [19][20][21][22][23]) and (iv) a protein scaffold for genetic engineering of new functionalities (e.g., [19,[24][25][26][27][28]).…”

Section: Introductionmentioning

confidence: 99%

Contribution of the heme propionate groups to the electron transfer and electrostatic properties of myoglobin

Lim

Sishta

Mauk

2006

Journal of Inorganic Biochemistry

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Contribution of the heme propionate groups to the electron transfer and electrostatic properties of myoglobin

Lim

Sishta

Mauk

2006

Journal of Inorganic Biochemistry

View full text Add to dashboard Cite

“…The concentrations of metMb and metHb are kept at a low level by an electron transportation chain that ends in a soluble cytochrome b 5 (cyt b 5 ) which mediates electron transfer between the flavin-containing cytochrome b 5 reductase and metMb/metHb [1,2,3]. Electron transfer between cyt b 5 and Mb/Hb in eukaryotes then is of critical importance, but the interaction between Mb/Hb and cyt b 5 is weak and little is known about the dynamical and structural features of the ET precursor protein complex.…”

Section: Introductionmentioning

confidence: 99%

Dynamic docking and electron transfer between myoglobin and cytochrome b 5

et al. 2002

View full text Add to dashboard Cite

The interaction of trypsin-digested bovine cytochrome b(5) (cyt b(5)) with horse heart myoglobin (Mb) and the interprotein electron transfer (ET) between these redox partners have been studied to gain better understanding of ET processes between weakly bound protein partners. The bimolecular rate constant ( k(2)) for photo-induced ET between zinc-substituted Mb (ZnMb) and cyt b(5) decreases with increasing ionic strength, consistent with the predominantly electrostatic character of this complex. The formation of a protein-protein complex has been confirmed and the binding affinities of metMb and ZnMb for cyt b(5) have been measured by two techniques: (1)H NMR titrations at pH 6.0 give binding constants of K(a) approximately (1.0+/-0.1)x10(3) M(-1) for metMb and K(a) approximately (0.75+/-0.1)x10(3) M(-1) for ZnMb; isothermal calorimetry gives K(a) approximately (0.35+/-0.1)x10(3) M(-1) for ZnMb. Brownian dynamic (BD) simulations show that cyt b(5) binds over a broad surface of Mb that includes its heme edge. The experimental results are described in terms of a dynamic docking model which proposes that Mb binds cyt b(5) in a large ensemble of protein binding conformations, not one or a few dominant ones, but that only a small subset are ET reactive. Aided by the BD simulations, this model explains why k(2) decreases with increasing pH: increasing pH not only weakens the binding affinity but also reduces the number of binding conformations with high ET reactivity.

show abstract

“…Cyt b 5 is the electron-carrier ‘repair’ protein that reduces met-Mb7 and met-Hb8,9 to their O 2 -carrying ferroheme forms. Studies of ET between Mb and cyt b 5 revealed that they react on a “Dynamic Docking” (DD) energy landscape (Fig 1, upper),10–12 on which binding and reactivity are uncoupled: binding is weak and involves an ensemble of nearly isoenergetic configurations, only a few of which are reactive; those few contribute negligibly to binding.…”

mentioning

confidence: 99%

Electrostatic Redesign of the [Myoglobin, Cytochrome b₅] Interface To Create a Well-Defined Docked Complex with Rapid Interprotein Electron Transfer

et al. 2009

View full text Add to dashboard Cite

Cyt b 5 is the electron-carrier 'repair' protein that reduces met-Mb and met-Hb to their O 2 -carrying ferroheme forms. Studies of electron transfer (ET) between Mb and cyt b 5 revealed that they react on a "Dynamic Docking" (DD) energy landscape on which binding and reactivity are uncoupled: binding is weak and involves an ensemble of nearly isoenergetic configurations, only a few of which are reactive; those few contribute negligibly to binding. We set the task of redesigning the surface of Mb so that its reaction with cyt b 5 instead would occur on a conventional 'simple docking' (SD) energy landscape, on which a complex exhibits a well-defined (set of) reactive binding configuration (s), with binding and reactivity thus no longer being decoupled. We prepared a myoglobin (Mb) triple mutant (D44K/D60K/E85K; Mb(+6)) substituted with Zn-deuteroporphyrin, and monitored cytochrome b 5 (cyt b 5 ) binding and electron transfer (ET) quenching of the 3 ZnMb(+6) triplet state. In contrast, to Mb(WT), the three charge-reversals around the 'front-face' heme edge of Mb(+6) have directed cyt b 5 to a surface area of Mb adjacent to its heme, created a well-defined, most-stable structure that supports good ET pathways, and apparently coupled binding and ET: both K a and k et are increased by the same factor of ~ 2×10 2 , creating a complex that exhibits a large ET rate constant, k et = 10 6 1 s −1 , and is in slow exchange (k off ≪ k et ). In short, these mutations indeed appear to have created the sought-for conversion from DD to simple docking (SD) energy landscapes.Interactions between macromolecules are fundamental to most of biology. The goal of understanding and controlling protein-protein interactions has inspired numerous efforts to modulate the binding within high-affinity complexes of known structure,1 -6 with most alterations serving to weaken binding. To begin such efforts at the other extreme, with a pair of proteins that bind weakly, and by altering them to create a well-defined, highly functional complex, offers a different level of challenge. We here report dramatic progress in creating bmh@northwestern.edu. Cyt b 5 is the electron-carrier 'repair' protein that reduces met-Mb 7 and met-Hb 8,9 to their O 2 -carrying ferroheme forms. Studies of ET between Mb and cyt b 5 revealed that they react on a "Dynamic Docking" (DD) energy landscape (Fig 1, upper),10 -12 on which binding and reactivity are uncoupled: binding is weak and involves an ensemble of nearly isoenergetic configurations, only a few of which are reactive; those few contribute negligibly to binding. The sharp contrast of such behavior with that for the conventional 'simple docking' (SD) energy landscape (Fig 1, lower), on which a complex exhibits a well-defined (set of) reactive binding configuration(s), led us to ask whether it was possible to redesign the surface of Mb so that its reaction with cyt b 5 instead would occur on a SD landscape, with binding and reactivity thus no longer being decoupled. NIH Public AccessThe low affinity of th...

show abstract

Inhibition of methemoglobin and metmyoglobin reduction by cobalt

Cited by 8 publications

References 16 publications

Contribution of the heme propionate groups to the electron transfer and electrostatic properties of myoglobin

Contribution of the heme propionate groups to the electron transfer and electrostatic properties of myoglobin

Dynamic docking and electron transfer between myoglobin and cytochrome b 5

Electrostatic Redesign of the [Myoglobin, Cytochrome b₅] Interface To Create a Well-Defined Docked Complex with Rapid Interprotein Electron Transfer

Contact Info

Product

Resources

About

Inhibition of methemoglobin and metmyoglobin reduction by cobalt

Cited by 8 publications

References 16 publications

Contribution of the heme propionate groups to the electron transfer and electrostatic properties of myoglobin

Contribution of the heme propionate groups to the electron transfer and electrostatic properties of myoglobin

Dynamic docking and electron transfer between myoglobin and cytochrome b 5

Electrostatic Redesign of the [Myoglobin, Cytochrome b5] Interface To Create a Well-Defined Docked Complex with Rapid Interprotein Electron Transfer

Contact Info

Product

Resources

About

Electrostatic Redesign of the [Myoglobin, Cytochrome b₅] Interface To Create a Well-Defined Docked Complex with Rapid Interprotein Electron Transfer